The objective of this research is to understand how secretagogues and secretory inhibitors regulate and coordinate the secretion and production of hydrogen ions from parietal cells isolated from the rat gastric mucosa. Enriched and purified parietal cells will be used to study secretagogue stimulation of acid secretion as well as related biochemical and cytoskeletal modifications associated with receptor activation. We plan to detect and more precisely characterize several cell membrane receptors using techniques of radiolabeled ligand binding. We also plan to examine biochemically the role of cyclic nucleotide metabolism, calmodulin, and cytoskeletal proteins in cell regulation by secretagogues. We will test our hypothesis that hydrogen ion production stimulated by acetylcholine and histamine is due to an interaction between calcium regulated intracellular events and accumulated cyclic AMP. Additionally, immunofluorescent cytochemical techniques will be used to localize components of both the cyclic nucleotide metabolic system and cytoskeletal structure which may be specifically involved in parietal cell function. This research should lead to a better understanding of the regulation of gastric acid secretion. Also, this research should identify alternative loci for possible pharmacological intervention necessary to control hydrogen ion secretion and peptic disease.